Purpose: to evaluate an efficacy of chemotherapy regimens R-DA-EPOCH-21 and R-BL-04 with and without autologous hematopoietic stem cells transplantation (auto-SCT) in newly diagnosed patients with High-Grade B-cell Lymphoma Double-hit and High-Grade B-cell Lymphoma Not Otherwise Specified.

Patients initially are randomized into 4 arms:

the first arm R-DA-EPOCH-21 the second arm R-BL-M-04 the third arm R-DA-EPOCH-21 + auto-SCT the fourth arm of R-BL-M-04 + auto-SCT Patients who achieved complete remission after 6 cycles of R-DA-EPOCH-21 or 4 cycles of R-BL-M-04 immunochemotherapy continue to be under observation (1st and 2nd arms) or continue treatment with Rituximab + BCNU+Etoposid+Ara-C+Melphalan (R-BEAM) followed by auto-SCT (3rd and 4th arms).

Patients who did not achieve complete remission with PET-CT data (4-5 Deauville points) are removed from the protocol and undergoing second-line therapy.

Inclusion Criteria:

1. First established the diagnosis of HGBL DH or HGBL-NOS.
2. No previous treatment with chemotherapy and/or radiation therapy of DLBCL
3. Informed consent of the patient.

Exclusion Criteria:

1. Pretreated lymphoma.
2. HIV-associated lymphoma
3. Congestive heart failure, unstable angina, severe cardiac arrhythmias and conduction disturbances, myocardial infarction.
4. Renal insufficiency (serum creatinine greater than 0.2 mmol/L) (except cases with specific kidney infiltration, urinary tract compression by tumour conglomerate or presence of uric acid nephropathy due to massive cytolysis syndrome).
5. Liver failure (except cases with liver tumour infiltration), acute hepatitis or active phase of chronic hepatitis B or C with serum bilirubin greater than 1.5 standards, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 standards, prothrombin index less than 70%.
6. Severe pneumonia (except cases with specific lungs infiltration), accompanied by respiratory failure (dyspnea > 30 in min., hypoxemia less than 70 mm Hg, when it is impossible to compensate situation in 2-3 days).
7. Life-threatening bleeding (gastrointestinal, intracranial), with exception of bleeding due to tumour infiltration of organs (stomach, intestines, uterus, etc.) and disseminated intravascular coagulation due to underlying disease complications after their successful conservative treatment.
8. Severe mental disorders (delusions, severe depressive syndrome and other manifestations of productive symptoms) not related to specific infiltration of a central nervous system.
9. Decompensated diabetes.

11. Pregnancy.